1. Field of the Invention
The present invention is directed to certain esters of m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohols, their pharmaceutically acceptable acid addition salts and certain intermediates useful in the preparation thereof. More particularly, the instant invention is directed to a novel synthesis for preparing the optically active (hereinafter R) or racemate form of the above-identified compounds.
Upon administration, these compounds will enzymatically "cleave" and release optically active m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol (phenylephrine), the therapeutically active moiety thereof.
2. Description of the Prior Art
U.S. Pat. No. 3,825,583 -- Hussain and Truelove, discloses and claims an ester of m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol, namely, m(3-)-pivaloxy-.alpha.-[methylamino)methyl]benzyl alcohol.
A review of the manner in which this compound is prepared readily reveals that a racemic mixture (a mixture containing both the biologically active and the biologically non-active isomer) is obtained. Since the R isomer is the only isomer exhibiting therapeutic activity, to date (R)-m-pivaloxy-.alpha.-[(methylamino)methyl]benzyl alcohol is normally administered in the form of a racemic mixture as the means to separate the optically active form from the racemic mixture is quite time consuming and expensive.
Therefore, a need exists for a means to synthesize the optically active form of certain m-aceyloxy-.alpha.-[(methylamino)methyl]benzyl alcohols of which m-pivaloxy-.alpha.-[(methylamino)methyl]benzyl alcohol is so among and thus avoid the need to (1) first obtain a racemic mixture, and (2) optionally, resolve the racemic mixture into the optically active isomer for administration or administer the racemic mixture, per se.
In addition to the foregoing, it is obviously apparent that since only the active isomer of the compounds described herein is therapeutically active, the dosage amount of a racemic mixture containing the same required to achieve therapeusis is much greater than that which would be required if the optically active form were administered, per se. Thus, an ancillary need exists for a means to synthesize the optically active isomer, per se, for the sake of minimizing the therapeutic dose required as well as to avoid any toxic reactions which may occur.